I'm very close to a usable setup for S/MIME. It took a lot of research, the documentation isn't great and seems a bit outdated in some cases (https://gitlab.com/muttmua/mutt/-/wikis/MuttGuide/UseSMIME - patch gpgme?), but the basics work.
Two questions remain now. The first, when using mutt with gpgme, are any of the gpg/gpg/certificate/smime related configuration variables still relevant? And if so, which? The question arises from this comment, "(If your .muttrc "source"s smime.rc or gpg.rc, you can comment out these lines, you don't need them any longer.)". at https://wiki.netbsd.org/users/wiz/mutt-smime/, and considering that in a typical setup, these variables are encapsulated in said files. The other question is, how do you send S/MIME encrypted email to unknown recipients. My understanding is that an S/MIME signature as received in email contains the complete certificate chain, and this enables one to send encrypted email to any recipient who's key is stored in the keybox. In the corporate scenario, where world and dog uses Outlook, you can send encrypted email to anyone in the organization at the press of a button. There must be some form of lookup involved, how can this be replicated with mutt?